Significance The development of new selective estrogen receptor modulators (SERMs) for thetreatment and prevention of osteoporosis, cardiovascular disease, and breast cancer are the focus of many investigations. The triphenylethylene FC 1271a prevents bone resorption in rats while having no or weak estrogen-like effects on the uterus, which makes it a good candidate drug for the prevention of osteoporosis. Objectives In the present study, we examined the pharmacokinetics, toxicity, and DNA adduct formation during single and chronic dosing of FC 1271a in the non-human primate Macaca mulatta. During single dosing, six female rhesus macaques were administered 35 mg/kg FC 1271a orally once a week for three weeks, which is a ten-fold higher dose than has been tested clinically. Pharmacokinetics, hematological toxicity, uterotropic effects, and serum cholesterol were monitored. During the chronic dosing study, six female monkeys were administered daily oral doses of 60 mg FC 1271a (approximately 9.7 mg/kg) for twelve weeks. Results In the single dose study, no hematological toxicities or uterotropic effects associated with the drug were found. Peak absorption was between four and five hours, and the elimination half-life was approximately 22 hours. Two metabolites of FC 1271a, one hydroxylated and one carboxylated, were detected by HPLC. Serum LDL levels appeared to be lowered while no other effects on serum lipids were observed. Chronic dosing resulted in no hematological toxicity and a lowering of LDL and increase in HDL. No endometrial effects were observed, and no DNA adducts were detected in the liver or endometrial biopsies collected during or after treatment. Future Directions Our results suggest that FC 1271a is non-toxic, has ideal pharmacokinetics, and has positive effects on serum cholesterol metabolism. Future studies of FC1271a effects on bone markers and bone density are being planned using the monkey model. KEYWORDS osteoporosis, SERMs', FC1271a, pharmacodynamics